| 1. |
- Berg, Stefan, 1959, et al.
(author)
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Autoinflammatory Disorders
- 2016
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In: Primary Immunodeficiency Diseases. - Berlin, Heidelberg : Springer. - 9783662529096 ; , s. 393-435
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Book chapter (peer-reviewed)
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| 2. |
- Berg, Stefan, 1959, et al.
(author)
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Autoinflammatory disorders
- 2017
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In: Primary Immunodeficiency Diseases. Definition, Diagnosis, and Management, 2nd ed.. - Berlin, Germany : Springer. - 9783662529072
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Book chapter (other academic/artistic)
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| 3. |
- Berg, Stefan, 1959, et al.
(author)
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Irregular Recurrent Fever : Chapter 113
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs. Nima Rezaei (red.). - Cham : Springer Nature Switzerland AG. - 9783030212629 ; , s. 617-621
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Book chapter (other academic/artistic)abstract
- Non-classifiable periodic fever syndromes are common Patients may have recurrent fevers or continuous chronic inflammation, together with different combinations of arthralgia/arthritis, mouth ulcers, lymphadenopathies, conjunctivitis, rashes, pleuritic pain, splenomegaly, hepatomegaly and abdominal pain Inheritance varies from no apparent pattern to autosomal dominant inheritance Many patients respond to colchicine as a reasonable first-line treatment
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| 4. |
- Berg, Stefan, 1959, et al.
(author)
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Long Episodes of Rash and Fever : Chapter 100
- 2019
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In: Pediatric Immunology : A Case-Based Collection with MCQs, Volume 2. Rezaei, N. (red.). - Switzerland AG : Springer Nature. - 9783030212629 ; , s. 527-531
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Book chapter (other academic/artistic)
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| 5. |
- Berg, Stefan, 1959, et al.
(author)
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Rash and Fever since Two Weeks of Age : Chapter 102
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs. Rezaei, N. (red.). - Cham : Springer Nature. - 9783030212629 ; , s. 539-543
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Book chapter (other academic/artistic)abstract
- Cryopyrin-associated periodic syndrome (CAPS) is an umbrella term today used for three formerly described conditions in order of increasing severity familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and chronic infantile neurologic cutaneous and articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID) CAPS is an autosomal dominant disease that starts early in life Mutations in CAPS give rise to a gain-of-function in the NLRP3 inflammasome Somatic mosaicism should be considered in patients with clinical CAPS and no mutation detected in the NLRP3 with Sanger sequencing CAPS is characterized by a varying degree of systemic inflammation, urticaria-like rash, musculoskeletal symptoms, and a risk of amyloidosis and neurologic sequelae Treatment with IL-1 blockade is generally very effective in CAPS
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| 6. |
- Berg, Stefan, 1959, et al.
(author)
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Sudden Dizziness, Somnolence and Diplopia : Chapter 111
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs.. - Cham : Springer Nature. - 9783030212629 ; , s. 603-609
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Book chapter (other academic/artistic)abstract
- Deficiency of adenosine deaminase 2 (DADA2) is a autosomal recessive disease caused by mutations in CECR1 Mutations in CECR1 cause a deficiency of the enzyme adenosine deaminase type 2 (ADA2) DADA2 phenotype has a wide spectrum and is characterized by the presence of three main features: (1) vascular inflammation, (2) immunodeficiency, and (3) coagulopathy, that may or may not overlap in the individual patient The vascular-inflammatory manifestations include livedo reticularis/racemosa, stroke, vasculitis, recurrent fever episodes and increased inflammatory markers The risk for stroke is high in DADA2 The phenotype may be almost indistinguishable to polyarteritis nodosa (PAN) TNF-blockade is an effective treatment for the vasculitis and inflammatory manifestations Patients with severe disease especially with hematological manifestations and immunodeficiency may benefit from HSCT
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| 7. |
- Björnsdottir, Halla, et al.
(author)
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Neutrophil NET formation is regulated from the inside by myeloperoxidase-processed reactive oxygen species.
- 2015
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In: Free radical biology & medicine. - : Elsevier BV. - 1873-4596 .- 0891-5849. ; 89, s. 1024-1035
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Journal article (peer-reviewed)abstract
- Neutrophil extracellular traps (NETs) are mesh-like DNA fibers clad with intracellular proteins that are cast out from neutrophils in response to certain stimuli. The process is thought to depend on reactive oxygen species (ROS) generated by the phagocyte NADPH-oxidase and the ROS-modulating granule enzyme myeloperoxidase (MPO), but when, how, and where these factors contribute is so far uncertain. The neutrophil NADPH-oxidase can be activated at different cellular sites and ROS may be produced and processed by MPO within intracellular granules, even in situations where a phagosome is not formed, e.g., upon stimulation with phorbol myristate acetate (PMA).
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| 8. |
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| 9. |
- McCreary, D., et al.
(author)
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Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation
- 2019
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In: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 2:10
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Journal article (peer-reviewed)abstract
- IMPORTANCE Neuroinflammatory disorders are a range of severe neurological disorders causing brain and spinal inflammation and are now increasingly recognized in the pediatric population. They are often characterized by marked genotypic and phenotypic heterogeneity, complicating diagnostic work in clinical practice and molecular diagnosis. OBJECTIVE To develop and evaluate a next-generation sequencing panel targeting genes causing neuroinflammation or mimicking neuroinflammation. DESIGN, SETTING, AND PARTICIPANTS Cohort study in which a total of 257 genes associated with monogenic neuroinflammation and/or cerebral vasculopathy, including monogenic noninflammatory diseases mimicking these entities, were selected. A customized enrichment capture array, the neuroinflammation gene panel (NIP), was created. Targeted high-coverage sequencing was applied to DNA samples taken from eligible patients referred to Great Ormond Street Hospital in London, United Kingdom, between January 1, 2017, and January 30, 2019, because of onset of disease early in life, family history, and/or complex neuroinflammatory phenotypes. MAIN OUTCOMES AND MEASURES The main outcome was the percentage of individuals with definitive molecular diagnoses, variant classification, and clinical phenotyping of patients with pathogenic variants identified using the NIP panel. The NIP panel was initially validated in 16 patients with known genetic diagnoses. RESULTS The NIP was both sensitive (95%) and specific (100%) for detection of known mutations, including gene deletions, copy number variants, small insertions and deletions, and somatic mosaicism with allele fraction as low as 3%. Prospective testing of 60 patients (30 [50%] male; median [range] age, 9.8 [0.8-20] years) presenting with heterogeneous neuroinflammatory phenotypes revealed at least 1 class 5 (clearly pathogenic) variant in 9 of 60 patients (15%); 18 of 60 patients (30%) had at least 1 class 4 (likely pathogenic) variant. Overall, a definitive molecular diagnosis was established in 12 of 60 patients (20%). CONCLUSIONS AND RELEVANCE The NIP was associated with molecular diagnosis in this cohort and complemented routine laboratory and radiological workup of patients with neuroinflammation. Unexpected genotype-phenotype associations in patients with pathogenic variants deviating from the classic phenotype were identified. Obtaining an accurate molecular diagnosis in a timely fashion informed patient management, including successful targeted treatment in some instances and early institution of hematopoietic stem cell transplantation in others.
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| 10. |
- Nanthapisal, S., et al.
(author)
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Deficiency of Adenosine Deaminase Type 2 A Description of Phenotype and Genotype in Fifteen Cases
- 2016
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191. ; 68:9, s. 2314-2322
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Journal article (peer-reviewed)abstract
- Objective. To describe the clinical features, genotype, and treatment in a series of subjects with confirmed adenosine deaminase 2 (ADA2) deficiency. Methods. All symptomatic subjects were referred for genetic testing for suspected ADA2 deficiency; relatives of index cases were also screened. Demographic, clinical, and laboratory characteristics and treatments were recorded. Genetic analyses included whole-exome sequencing in 4 subjects and Sanger sequencing of CECR1 (the gene for cat eye syndrome chromosome region candidate 1) in all subjects. Assays for ADA2 enzyme activity and quantitative polymerase chain reaction analysis of CECR1 messenger RNA (mRNA) were also performed. Results. We identified 15 subjects with ADA2 deficiency, 5 of whom were asymptomatic (relatives of index cases; ages 5-42 years). Homozygous or compound heterozygous mutations in CECR1 were identified in all subjects. Phenotypic manifestations in the patients with symptomatic ADA2 deficiency included livedo racemosa (73.3%), neurologic involvement (53.3%), and immunodeficiency (46.7%). CECR1 mRNA expression in 8 subjects, including 5 who were presymptomatic, was significantly lower than in healthy controls (P=0.0016). Subjects with ADA2 deficiency (with or without symptoms) also had lower ADA2 enzyme activity compared to healthy pediatric controls (P<0.0001) and patients with sporadic (nonfamilial) childhood polyarteritis nodosa (PAN) without CECR1 mutation (P= 0.0108). Anti-tumor necrosis factor therapy was required in 9 of the 10 symptomatic subjects. Conclusion. The clinical manifestations of ADA2 deficiency ranged in severity from limited cutaneous involvement to severe multisystemic vasculitis; one-third of our cases (5 of 15) were currently asymptomatic, and required close monitoring. We recommend CECR1 screening for unaffected siblings of index cases, cases of familial vasculitis, and cases of PAN that is resistant to standard treatment.
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| 11. |
- Rydenman, Karin, 1982, et al.
(author)
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Chapter 104. Recurrent Fever and Sore Throat
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs. Rezaei N. (red.). - Cham : Springer. - 9783030212612 ; , s. 553-559
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Book chapter (other academic/artistic)
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| 12. |
- Rydenman, Karin, 1982, et al.
(author)
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PFAPA syndrome - An important differential diagnosis in children with recurrent fever : PFAPA-syndrom – en viktig differentialdiagnos hos barn med återkommande feberepisoder.
- 2019
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In: Läkartidningen. - 1652-7518. ; 116
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Research review (peer-reviewed)abstract
- Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is the most common autoinflammatory disorder among children in many parts of the world and an important differential diagnosis in children presenting with recurrent fever episodes. Commonly, PFAPA has an onset under the age of 5 years. Fever episodes in PFAPA usually last 3-6 days and are associated with one or more of the cardinal symptoms aphthous stomatitis, pharyngitis and cervical adenitis. The fever episodes typically recur with an interval of 3-6 weeks, often with a striking regularity. During the episodes, the patient has elevated inflammatory variables such as CRP and serum amyloid A (SAA) and may sometimes have additional symptoms such as abdominal pain, nausea and leg pain. Between the fever episodes, the patient is typically free of symptoms with normalized inflammatory variables and grows normally. Awareness and recognition of PFAPA is key to providing the patient with adequate treatment and avoiding misdiagnosis.
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| 13. |
- Sparud Lundin, Carina, 1964, et al.
(author)
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From uncertainty to gradually managing and awaiting recovery of a periodic condition- a qualitative study of parents´ experiences of PFAPA syndrom
- 2019
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 19:99, s. 1-9
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Journal article (peer-reviewed)abstract
- BackgroundThe prevalence of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is unknown. Although an uncommon condition, it is considered to be the most common autoinflammatory disease among children in many parts of the world. The knowledge of the consequences of the recurrent fever episodes for the child and its family are limited. This study explores the experiences of parents regarding the impact of the disease on the child's general well-being, the family's situation and how the family handles the associated challenges.MethodsA qualitative approach was used, applying a modified version of Grounded theory for design, data collection and analysis. Data was collected from two different sources: communication between parents of children with PFAPA in a closed Facebook group and face-to face interviews with one of the parents of children diagnosed with PFAPA (6 mothers and 2 fathers).ResultsParents described a lengthy process of how everyday life becomes affected by their child's recurrent fever episodes. This process is depicted in the following Grounded Theory core category: From uncertainty to gradually managing and awaiting recovery. The categories Uncertainty, Assurance, Gradually managing and Recovery describe the experienced illness trajectory. The illness representation illustrates the experiences/impacts of the periodic condition in the subcategories: Harmlessness-Severity, Disclosure of diagnosis, Impact on daily life and Regularity-Unpredictability. The children's well-being was highly affected by the symptoms during episodes. Parents experienced increased stress with constant fatigue, social constraints of family life and restricted career opportunities. Nevertheless, hope of recovery was constantly present.ConclusionsPFAPA is associated with a considerable burden on the child and the parents in daily life. Obtaining a diagnosis enables parents to move from a state of uncertainty towards a sense of coherence while awaiting recovery. Because of limited general knowledge of the condition and its impact on daily life, health care professionals need to become aware of the parents' efforts to mitigate the consequences of the recurrent episodes for the child and for the family as a whole.
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| 14. |
- Wekell, Per, et al.
(author)
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Familial mediterranean fever – An important disease in a globalised world : Familjär medelhavsfeber - viktig sjukdom i en globaliserad värld - Särskilt vanlig hos personer från östra Medelhavsområdet.
- 2016
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In: Läkartidningen. - 1652-7518. ; 113
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Research review (peer-reviewed)abstract
- Familial Mediterranean fever - an important disease in a globalised world Familial Mediterranean fever (FMF) is characterized by recurrent febrile attacks during 1/2-3 days associated with peritonitis, pleuritis and arthritis. FMF is the most common monogenic autoinflammatory disease in the world, with over 100 000 affected individuals. It is particularly common in individuals with an origin in the eastern Mediterranean Basin, where the disease has a prevalence of 100-200 per 100 000. The gene for FMF (MEFV) was identified in 1997 with an autosomal recessive inheritance; however, a significant proportion (≈25%) of clinical patients lack two mutations. MEFV codes for the protein pyrin, whose exact function still needs to be defined. The most serious complication of FMF is amyloid A amyloidosis, in particular renal amyloidosis. FMF is efficiently treated with daily doses of colchicine resulting in an almost normal life expectancy and amyloidosis confined to non-compliant patients. In today's globalized world we need to adapt to a new context that includes inherited conditions, which have historically been uncommon in our part of the world. One of these conditions is FMF, that should primarily be suspected in individuals with an origin in the eastern Mediterranean Basin and recurrent attacks of fever.
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| 15. |
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| 16. |
- Wekell, Per, et al.
(author)
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Periodic Fever Syndrome and Developmental Delay : Chapter 98
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs. Nima Rezaei (red.). - Cham : Springer Nature Switzerland AG. - 9783030212612 ; , s. 515-519
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Book chapter (other academic/artistic)abstract
- The key to diagnosis of mevalonate kinase deficiency, hyper-IgD syndrome (MKD/HIDS) is recurrent fever attacks of 4–6 days, associated with aphthous stomatitis, enlargement of lymph nodes, splenomegaly, abdominal pain, diarrhea, and rash MKD is a rare autosomal recessive disease caused by mutations in the MVK gene leading to reduced mevalonate kinase activity Extremely low MVK activity leads to mevalonic aciduria (complete MKD or MVA) associated with developmental delay, progressive ataxia and decreased life expectancy in addition to febrile attacks Treatment depends on the severity of the condition and includes: on demand treatment with glucocorticoids on demand or continuous treatment with IL-1 blockade allogeneic hematopoietic stem cell transplantation in mevalonic aciduria In partial MKD/HIDS, episodes often decrease in severity with age
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| 17. |
- Wekell, Per, et al.
(author)
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Prolonged Fever and Swollen Joints : Chapter 106
- 2019
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In: Pediatric Immunology A Case-Based Collection with MCQs. Nima Rezaei (red.). - Cham : Springer Nature Switzerland AG. - 9783030212629 ; , s. 565-573
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Book chapter (other academic/artistic)abstract
- The diagnosis of systemic onset juvenile idiopathic arthritis (SoJIA) is based on clinical features including: prolonged quotidian fever, erythematous rash during fever spikes, generalized lymph node enlargement, arthralgia/arthritis and splenomegaly Glucocorticoids are the first-line treatment of SoJIA Approximately 10% of patients with SoJIA develop macrophage activation syndrome (MAS) associated with significant mortality The main complication of SoJIA is MAS characterised by: Clinical features such as continuous fever, petechial rash, hepatosplenomegaly and compromised circulation, laboratory findings such as cytopenias in two or more cell lines, increased ferritin, liver transaminases, lactate dehydrogenase and triglycerides There are no evidence-based treatment guidelines for MAS in SoJIA. Early expert advice should be sought. High-dose intravenous methylprednisolone is recommended as a first-line treatment.
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| 18. |
- Wekell, Per, et al.
(author)
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Recurrent Chest Pain : Chapter 112
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs. Nima Rezaei (red.). - Cham : Springer Nature Switzerland AG. - 9783030212629 ; , s. 611-616
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Book chapter (other academic/artistic)abstract
- Recurrent pericarditis is diagnosed in a patient with acute pericarditis relapse after a symptom-free interval of 4–6 weeks or longer First-line treatment for recurrent pericarditis is cycloxygenase-inhibitors and colchicine Corticosteroid should be avoided in children due to their adverse side-effects, increased risk of relapse and effects on growth Long-term prognosis for children with recurrent pericarditis is generally good
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| 19. |
- Wekell, Per, et al.
(author)
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Recurrent Febrile Episodes and Abdominal Pain : Chapter 96
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs. Nima Rezaei (red.). - Cham : Springer Nature Switzerland AG. - 9783030212612 ; , s. 501-510
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Book chapter (other academic/artistic)abstract
- Familial Mediterranean fever (FMF) should be suspected in children with recurrent, fever attacks of short duration, 6 hours-3 days, associated with peritonitis, pleuritis and/or arthritis FMF is most common in populations with eastern Mediterranean origin FMF is considered an autosomal recessive disease, yet biallelic mutations are not always identified Colchicine is the drug-of-choice that effectively prevents FMF attacks and amyloidosis Secondary amyloidosis is the main long-term complication in untreated patients.
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| 20. |
- Wekell, Per, et al.
(author)
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Review of autoinflammatory diseases, with a special focus on periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome.
- 2016
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In: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 105:10, s. 1140-51
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Research review (peer-reviewed)abstract
- There have been remarkable developments in the field of autoinflammatory diseases over the last 20 years. Research has led to definitions of new conditions, increased understanding of disease mechanisms and specific treatment. The polygenic autoinflammatory condition of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is the most common autoinflammatory disorder among children in many parts of the world. The clinical features often include clockwork regularity of episodes, prompt responses to corticosteroids and therapeutic effects of tonsillectomy, but the disease mechanisms are largely unknown.
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| 21. |
- Wekell, Per, et al.
(author)
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Skeletal Pain in Knee and Clavicle : Chapter 107
- 2019
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In: Pediatric Immunology. A Case-Based Collection with MCQs. Nima Rezaei (red.). - Cham : Springer Nature Switzerland AG. - 9783030212629 ; , s. 575-581
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Book chapter (other academic/artistic)abstract
- Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is characterized by sterile bone inflammation commonly located in the metaphysis of long bones, the clavicle, spine, and the pelvisBone lesions can be both symptomatic and asymptomatic CNO/CRMO is a diagnosis of exclusion and a bone biopsy is often needed to confirm the diagnosis and exclude other disorders Empirical treatment options include; Cox-inhibitors (NSAIDs), glucocorticoids, anti-TNF agents and bisphosphonates
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| 22. |
- Wekell, Per, et al.
(author)
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Toward an Inclusive, Congruent, and Precise Definition of Autoinflammatory Diseases.
- 2017
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In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Journal article (peer-reviewed)abstract
- Autoinflammatory disease was introduced as a concept in 1999, demarcating an entirely new group of diseases in clinical, immunological, and conceptual terms. During recent years, the preconditions for the definition of autoinflammatory conditions have changed. This includes the recent discovery of a number of monogenic autoinflammatory conditions with complex phenotypes that combine autoinflammation with defects of the adaptive and/or innate immune system, resulting in the occurrence of infection, autoimmunity, and/or uncontrolled hyperinflammation in addition to autoinflammation. Further, there are strong indications that classical IL-1-driven autoinflammatory diseases are associated with activation of adaptive immunity. As suggested by this development, we are of the opinion that an all-encompassing definition of autoinflammatory diseases should regard autoinflammatory conditions and innate dysregulation as inseparable and integral parts of the immune system as a whole. Hence, in this article, we try to advance the conceptual understanding of autoinflammatory disease by, proposing a modification of the definition by Daniel Kastner et al., which allows for a congruent and precise description of conditions that expand the immunological spectrum of autoinflammatory disease.
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